tbuckley/cabot-search huggingface dataset:
Tat-NTS peptide protects neurons against cerebral ischemia-reperfusion injury via ANXA1 SUMOylation in microglia
Authors: Huijuan Zhou, Lulu Yan, Hezhou Huang, Xing Li, Qian Xia, Lu Zheng, Bin Shao, Qian Gao, Ning Sun, Jing Shi
Journal: Theranostics (2023)

Rationale:Recent studies indicate that microglial activation and the resulting inflammatory response could be potential targets of adjuvant therapy for ischemic stroke.Many studies have emphasized a well-established function of Annexin-A1 (ANXA1) in the immune system, including the regulation of microglial activation.Nevertheless, few therapeutic interventions targeting ANXA1 in microglia for ischemic stroke have been conducted.In the present study, Tat-NTS, a small peptide developed to prevent ANXA1 from entering the nucleus, was utilized.We discovered the underlying mechanism that Tat-NTS peptide targets microglial ANXA1 to protect against ischemic brain injury.Methods: Preclinical studies of ischemic stroke were performed using an oxygen-glucose deprivation and reperfusion (OGD/R) cell model in vitro and the middle cerebral artery occlusion (MCAO) animal model of ischemic stroke in vivo.Confocal imaging and 3D reconstruction analyses for detecting the protein expression and subcellular localization of microglia in vivo.Co-immunoprecipitation (Co-IP), immunoblotting, ELISA, quantitative real-time PCR (qRT-PCR), Luciferase reporter assay for determining the precise molecular mechanism.Measurement on the cytotoxicity of Tat-NTS peptide for microglia was assessed by CCK-8 and LDH assay.TUNEL staining was used to detect the microglia conditioned medium-mediated neuronal apoptosis.Adeno-associated viruses (AAVs) were injected into the cerebral cortex, striatum and hippocampal CA1 region of adult male Cx3cr1-Cre mice, to further verify the neurofunctional outcome and mechanism of Tat-NTS peptide by TTC staining, the modified Neurological Severity Score (mNSS) test, the open field test (OFT), the novel object recognition task (NORT), the Morris water maze (MWM) test, the long-term potentiation (LTP) and the Transmission electron microscopy (TEM). Results:It was observed that administration of Tat-NTS led to a shift of subcellular localization of ANXA1 in microglia from the nucleus to the cytoplasm in response to ischemic injury.Notably, this shift was accompanied by an increase in ANXA1 SUMOylation in microglia and a transformation of microglia towards an anti-inflammatory phenotype.We confirmed that Tat-NTS-induced ANXA1 SUMOylation in microglia mediated IKKα degradation via NBR1-dependent selective autophagy, then blocking the activation of the NF-κB pathway.As a result, the expression and release of the pro-inflammatory factors IL-1β and TNF-α were reduced in both in vitro and in vivo experiments.Furthermore, we found that Tat-NTS peptide's protective effect on microglia relieved ischemic neuron apoptosis.Finally, we Ivyspring
Bile acid-containing lipid nanoparticles enhance extrahepatic mRNA delivery
Authors: Savan K. Patel, Margaret M. Billingsley, Alvin J. Mukalel, Ajay S. Thatte, Alex G. Hamilton, Ningqiang Gong, Rakan El-Mayta, Hannah C. Safford, Maria Merolle, Michael J. Mitchell
Journal: Theranostics (2023)

Lipid nanoparticles (LNPs) have emerged as a viable, clinically-validated platform for the delivery of mRNA therapeutics. LNPs have been utilized as mRNA delivery systems for applications including vaccines, gene therapy, and cancer immunotherapy. However, LNPs, which are typically composed of ionizable lipids, cholesterol, helper lipids, and lipid-anchored polyethylene glycol, often traffic to the liver which limits the therapeutic potential of the platform. Several approaches have been proposed to resolve this tropism such as post-synthesis surface modification or the addition of synthetic cationic lipids.
Improving susceptibility of neuroendocrine tumors to radionuclide therapies: personalized approaches towards complementary treatments
Authors: Susan Richter, Charlotte Steenblock, Alessa Fischer, Sandy Lemm, Christian G. Ziegler, Nicole Bechmann, Svenja Nölting, Jens Pietzsch, Martin Ullrich
Journal: Theranostics (2023)

Radionuclide therapies are an important tool for the management of patients with neuroendocrine neoplasms (NENs). Especially [
Tumor-on-a-chip models combined with mini-tissues or organoids for engineering tumor tissues
Authors: Hanjun Hwangbo, SooJung Chae, Wonjin Kim, Seoyul Jo, Geun Hyung Kim
Journal: Theranostics (2023)

The integration of tumor-on-a-chip technology with mini-tissues or organoids has emerged as a powerful approach in cancer research and drug development. This review provides an extensive examination of the diverse biofabrication methods employed to create mini-tissues, including 3D bioprinting, spheroids, microfluidic systems, and self-assembly techniques using cell-laden hydrogels. Furthermore, it explores various approaches for fabricating organ-on-a-chip platforms. This paper highlights the synergistic potential of combining these technologies to create tumor-on-a-chip models that mimic the complex tumor microenvironment and offer unique insights into cancer biology and therapeutic responses.
Risk of cancer for patients with rheumatoid arthritis versus general population: a national claims database cohort study
Authors: Maxime Beydon, Sandrine Pinto, Yann De Rycke, Bruno Fautrel, Xavier Mariette, Raphaèle Seror, Florence Tubach
Journal: The Lancet Regional Health - Europe (2023)

Older studies uncovered an increased risk of cancer in patients with rheumatoid arthritis between 10% and 30% compared to the general population, with a lack of data concerning infrequent cancers. In recent year, major therapeutic breakthroughs might have affected this risk of cancer by mitigating disease activity or on the contrary by impairing antitumoral immune response. The objectives of this study are to compare cancer risk in patients with treated rheumatoid arthritis to the general population, in all treated patients and according to treatment exposure.This is a nationwide population-based study within the French national claims database "Système National des Données de Santé" (SNDS) between January 1st 2010 and December 31st 2020, to estimate the age and sex-standardized incidence ratios of cancer (all sites and site specific) of treated rheumatoid arthritis patients, with the French population as reference (by use of the French Network of Population-Based Cancer Registries [FRANCIM]).During the study period, 257,074 treated patients with rheumatoid arthritis contributed to a total of 2,098,238 person-years for the main analysis. The all-cancer risk was increased in rheumatoid arthritis patients, with a SIR (Standardized Incidence Ratio) of 1.20 (95% CI [1.17-1.23]). This risk was increased particularly for lung (SIR 1.41, 95% CI [1.36-1.46], bladder (SIR 2.38 95% CI [2.25-2.51]), cervix (SIR 1.80, 95% CI [1.62-2.01]), prostate (SIR 1.08, 95% CI [1.04, 1.13]) cancers, melanoma (SIR 1.37, 95% CI [1.29-1.46]), diffuse large B cell lymphoma (SIR 1.79, 95% CI [1.63-1.96], multiple myeloma (SIR 1.42, 95% CI [1.27-1.60]) and Hodgkin's lymphoma (SIR 2.73, 95% CI [2.31-3.23]). Some cancers were less frequent than in the general population such as pancreatic (SIR 0.90, 95% CI [0.83-0.97]) as well as breast and endometrial cancers (SIR 0.91, 95% CI [0.88-0.94] and SIR 0.77, 95% CI [0.71-0.84] respectively). Although we observed a modest but significant relative increase of all-cancer risk over-time in rheumatoid arthritis patients, there was a trend towards a decrease in risk of non-Hodgkin's lymphoma. Patients treated with rituximab were the patients displaying the highest risk of cancer.Compared to the general population, treated rheumatoid arthritis patients were at greater risk of all-cancer and some site specific cancers, except for breast, pancreatic and endometrial cancers which were less frequent than in the general population.This work was supported by unrestricted grants from the InCA (national institute against cancer) and AP-HP (Assistance Publique des Hôpitaux de Paris).
Cardiac Troponin Assays to Distinguish Between Acute and Chronic Myocardial Injury
Authors: Nils A. Sörensen, Linlin Guo, Paul M. Haller, Farnaz Dehkordi, Jonas Lehmacher, Alina Schock, Betül Toprak, Tanja Zeller, Raphael Twerenbold, Johannes T. Neumann
Journal: Journal of the American College of Cardiology (2023)
Cusatuzumab plus azacitidine in newly diagnosed acute myeloid leukaemia ineligible for intensive chemotherapy (CULMINATE): part one of a randomised, phase 2, dose optimisation study
Authors: Thomas Pabst, Cristina Papayannidis, Fatih Demirkan, Vadim Doronin, Laura M Fogliatto, Christina Guttke, Emmanuel Gyan, Nada Hamad, Pilar Herrera, Anna Hultberg, Julie Jacobs, Amy J Johnson, Angélique Langlois, Xuewen Ma, Giovanni Martinelli, Montserrat Arnan, Rouven Müller, Kerri Nottage, Yishai Ofran, Muhit Özcan, Olga Samoilova, Jaszianne A Tolbert, Géralyn C Trudel, Liang Xiu, Norbert Vey, Andrew H Wei
Journal: The Lancet Haematology (2023)
Imaging Brain Injury in Former National Football League Players
Authors: Leah H. Rubin, Yong Du, Shannon Eileen Sweeney, Riley O’Toole, Cykyra L. Thomas, Adeline G. Zandi, Laura K. Shinehouse, Mary Katherine Brosnan, Hwanhee Nam, Michael E. Burke, Samantha C. Bureau, Jessica J. Kilgore, Mark Yoon, Ana R. Soule, Wojciech G. Lesniak, Il Minn, Steven P. Rowe, Daniel P. Holt, Andrew W. Hall, William B. Mathews, Gwenn S. Smith, Christopher J. Nowinski, Michael Kassiou, Robert F. Dannals, Martin G. Pomper, Jennifer M. Coughlin
Journal: JAMA Network Open (2023)

Pilot studies that involved early imaging of the 18 kDa translocator protein (TSPO) using positron emission tomography (PET) indicated high levels of TSPO in the brains of active or former National Football League (NFL) players. If validated further in larger studies, those findings may have implications for athletes involved in collision sport.To test for higher TSPO that marks brain injury and repair in a relatively large, unique cohort of former NFL players compared with former elite, noncollision sport athletes.This cross-sectional study used carbon 11-labeled N,N-diethyl-2-(4-methoxyphenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-acetamide positron emission tomography ([11C]DPA-713 PET) data from former NFL players within 12 years of last participation in the NFL and elite noncollision sport athletes from across the US. Participants were enrolled between April 2018 and February 2023.Regional [11C]DPA-713 total distribution volume from [11C]DPA-713 PET that is a measure of regional brain TSPO; regional brain volumes on magnetic resonance imaging; neuropsychological performance, including attention, executive function, and memory domains.This study included 27 former NFL players and 27 former elite, noncollision sport athletes. Regional TSPO levels were higher in former NFL players compared with former elite, noncollision sport athletes (unstandardized β coefficient, 1.08; SE, 0.22; 95% CI, 0.65 to 1.52; P < .001). The magnitude of the group difference depended on region, with largest group differences in TSPO in cingulate and frontal cortices as well as hippocampus. Compared with noncollision sport athletes, former NFL players performed worse in learning (mean difference [MD], -0.70; 95% CI, -1.14 to -0.25; P = .003) and memory (MD, -0.77; 95% CI, -1.24 to -0.30; P = .002), with no correlation between total gray matter TSPO and these cognitive domains.In this cross-sectional study using [11C]DPA-713 PET, higher brain TSPO was found in former NFL players compared with noncollision sport athletes. This finding is consistent with neuroimmune activation even after cessation of NFL play. Future longitudinal [11C]DPA-713 PET and neuropsychological testing promises to inform whether neuroimmune-modulating therapy may be warranted.
Interaction of heart failure and stroke: A clinical consensus statement of the <scp>ESC</scp> Council on Stroke, the Heart Failure Association (<scp>HFA</scp>) and the <scp>ESC</scp> Working Group on Thrombosis
Authors: Wolfram Doehner, Michael Böhm, Giuseppe Boriani, Christina Christersson, Andrew J.S. Coats, Karl Georg Haeusler, Ian D. Jones, Gregory Y.H. Lip, Marco Metra, George Ntaios, Gianluigi Savarese, Eduard Shantsila, Gemma Vilahur, Giuseppe Rosano
Journal: European Journal of Heart Failure (2023)

ABSTRACT Heart failure (HF) is a major disease in our society that often presents with multiple comorbidities with mutual interaction and aggravation. The comorbidity of HF and stroke is a high risk condition that requires particular attention to ensure early detection of complications, efficient diagnostic workup, close monitoring, and consequent treatment of the patient. The bi‐directional interaction between the heart and the brain is inherent in the pathophysiology of HF where HF may be causal for acute cerebral injury, and – in turn – acute cerebral injury may induce or aggravate HF via imbalanced neural and neurovegetative control of cardiovascular regulation. The present document represents the consensus view of the ESC Council on Stroke, the Heart Failure Association and the ESC Working Group on Thrombosis to summarize current insights on pathophysiological interactions of the heart and the brain in the comorbidity of HF and stroke. Principal aspects of diagnostic workup, pathophysiological mechanisms, complications, clinical management in acute conditions and in long‐term care of patients with the comorbidity are presented and state‐of‐the‐art clinical management and current evidence from clinical trials is discussed. Beside the physicians perspective, also the patients values and preferences are taken into account. Interdisciplinary cooperation of cardiologists, stroke specialists, other specialists and primary care physicians is pivotal to ensure optimal treatment in acute events and in continued long‐term treatment of these patients. Key consensus statements are presented in a concise overview on mechanistic insights, diagnostic workup, prevention and treatment to inform clinical acute and continued care of patients with the comorbidity of HF and stroke.
Single-Cell Meta-Analysis of Neutrophil Activation in Kawasaki Disease and Multisystem Inflammatory Syndrome in Children Reveals Potential Shared Immunological Drivers
Authors: Jan Vincent B. Beltran, Fang-Ping Lin, Chaw-Liang Chang, Tai-Ming Ko
Journal: Circulation (2023)

Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C) share similar clinical manifestations, including cardiovascular complications, suggesting similar underlying immunopathogenic processes. Aberrant neutrophil activation may play a crucial role in the shared pathologies of KD and MIS-C; however, the associated pathogenic mechanisms and molecular drivers remain unknown.
Care of Young Children With Diabetes in the Childcare and Community Setting: A Statement of the American Diabetes Association
Authors: Christine March, Jennifer Sherman, Raveendhara R. Bannuru, Aaron Fischer, Robert A. Gabbay, Henry Rodriguez, Janet Rodriguez, Jill Weissberg-Benchell, Crystal Woodward, Nuha A. ElSayed
Journal: Diabetes Care (2023)

Diabetes management in children extends from the home to other settings where children spend a significant portion of their waking hours. For young children (generally, aged &amp;lt;5 years) with diabetes, this includes childcare centers. Given their age and developmental stage, young children require a carefully thought-out, proactive diabetes care plan for the childcare setting, developed jointly by the health care provider and parents/guardians, and implemented by childcare staff. In the U.S., federal laws and some state laws protect the rights of children with diabetes in childcare and other settings to ensure they receive appropriate assistance with the diabetes management and care. This American Diabetes Association (ADA) Statement addresses the legal rights of children in the childcare setting, outlines the current best practices for diabetes care, and provides resources and responsibilities for parents/guardians, childcare providers, and health care providers. The ADA intends for these tools and information to support the health and well-being of young children with diabetes and offer helpful guidance to those caring for them.
How to use the Surveillance, Epidemiology, and End Results (SEER) data: research design and methodology
Authors: Wen-Qiang Che, Yuan-Jie Li, Chi-Kwan Tsang, Yu-Jiao Wang, Zheng Chen, Xiang-Yu Wang, An-Ding Xu, Jun Lyu
Journal: Military Medical Research (2023)

In the United States (US), the Surveillance, Epidemiology, and End Results (SEER) program is the only comprehensive source of population-based information that includes stage of cancer at the time of diagnosis and patient survival data. This program aims to provide a database about cancer incidence and survival for studies of surveillance and the development of analytical and methodological tools in the cancer field. Currently, the SEER program covers approximately half of the total cancer patients in the US. A growing number of clinical studies have applied the SEER database in various aspects. However, the intrinsic features of the SEER database, such as the huge data volume and complexity of data types, have hindered its application. In this review, we provided a systematic overview of the commonly used methodologies and study designs for retrospective epidemiological research in order to illustrate the application of the SEER database. Therefore, the goal of this review is to assist researchers in the selection of appropriate methods and study designs for enhancing the robustness and reliability of clinical studies by mining the SEER database.
Short‐term effects of sacubitril/valsartan therapy on myocardial oxygen consumption and energetic efficiency of cardiac work in heart failure with reduced ejection fraction: A randomized controlled study
Authors: Sergey V. Nesterov, Johanna Räty, Wail Nammas, Teemu Maaniitty, Xavier Galloo, Jan Stassen, Sanna Laurila, Tuija Vasankari, Jenni Huusko, Jeroen J. Bax, Antti Saraste, Juhani Knuuti
Journal: European Journal of Heart Failure (2023)

We sought to evaluate the mechanism of angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan therapy and compare it with a valsartan-only control group in patients with heart failure with reduced ejection fraction (HFrEF).
Time to treat the climate and nature crisis as one indivisible global health emergency
Authors: Kamran Abbasi, Parveen Ali, Virginia Barbour, Thomas Benfield, Kirsten Bibbins-Domingo, Stephen Hancocks, Richard Horton, Laurie Laybourn-Langton, Robert Mash, Peush Sahni, Wadeia Mohammad Sharief, Paul Yonga, Chris Zielinski
Journal: Journal of the Royal Society of Medicine (2023)
An Electroconductive and Antibacterial Adhesive Nanocomposite Hydrogel for High‐Performance Skin Wound Healing
Authors: Wen Zheng, Wenyue Yang, Wenlong Wei, Ziru Liu, Pier‐Luc Tremblay, Tian Zhang
Journal: Advanced Healthcare Materials (2023)

Multifunctional hydrogel adhesives inhibiting infections and enabling the electrical stimulation (ES) of tissue reparation are highly desirable for the healing of surgical wounds and other skin injuries. Herein, a therapeutic nanocomposite hydrogel is designed by integrating β-cyclodextrin-embedded Ag nanoparticles (
Characteristics and outcomes of patients with atrial versus ventricular secondary tricuspid regurgitation undergoing tricuspid transcatheter edge‐to‐edge repair – Results from the <scp>TriValve</scp> registry
Authors: Giulio Russo, Luigi P Badano, Marianna Adamo, Hannes Alessandrini, Martin Andreas, Daniel Braun, Kim A. Connelly, Paolo Denti, Rodrigo Estevez‐Loureiro, Neil Fam, Mara Gavazzoni, Rebecca T. Hahn, Claudia Harr, Joerg Hausleiter, Dominique Himbert, Daniel Kalbacher, Edwin Ho, Azeem Latib, Edith Lubos, Sebastian Ludwig, Philipp Lurz, Vanessa Monivas, Georg Nickenig, Daniela Pedicino, Giovanni Pedrazzini, Alberto Pozzoli, Denise Pires Marafon, Roberta Pastorino, Fabien Praz, Joseph Rodes‐Cabau, Christian Besler, Joachim Schofer, Andrea Scotti, Kerstin Piayda, Horst Sievert, Gilbert H.L. Tang, Holger Thiele, Florian Schlotter, Ralph Stephan von Bardeleben, John Webb, Stephan Windecker, Martin Leon, Francesco Maisano, Marco Metra, Maurizio Taramasso
Journal: European Journal of Heart Failure (2023)
Association between pathologic response and survival after neoadjuvant therapy in lung cancer
Authors: Julie Stein Deutsch, Ashley Cimino-Mathews, Elizabeth Thompson, Mariano Provencio, Patrick M. Forde, Jonathan Spicer, Nicolas Girard, Daphne Wang, Robert A. Anders, Edward Gabrielson, Peter Illei, Jaroslaw Jedrych, Ludmila Danilova, Joel Sunshine, Keith M. Kerr, Mia Tran, Judith Bushong, Junliang Cai, Vipul Devas, Jaclyn Neely, David Balli, Tricia R. Cottrell, Alex S. Baras, Janis M. Taube
Journal: Nature Medicine (2023)

Abstract Neoadjuvant immunotherapy plus chemotherapy improves event-free survival (EFS) and pathologic complete response (0% residual viable tumor (RVT) in primary tumor (PT) and lymph nodes (LNs)), and is approved for treatment of resectable lung cancer. Pathologic response assessment after neoadjuvant therapy is the potential analog to radiographic response for advanced disease. However, %RVT thresholds beyond pathologic complete response and major pathologic response (≤10% RVT) have not been explored. Pathologic response was prospectively assessed in the randomized, phase 3 CheckMate 816 trial (NCT02998528), which evaluated neoadjuvant nivolumab (anti-programmed death protein 1) plus chemotherapy in patients with resectable lung cancer. RVT, regression and necrosis were quantified (0–100%) in PT and LNs using a pan-tumor scoring system and tested for association with EFS in a prespecified exploratory analysis. Regardless of LN involvement, EFS improved with 0% versus &gt;0% RVT-PT (hazard ratio = 0.18). RVT-PT predicted EFS for nivolumab plus chemotherapy (area under the curve = 0.74); 2-year EFS rates were 90%, 60%, 57% and 39% for patients with 0–5%, &gt;5–30%, &gt;30–80% and &gt;80% RVT, respectively. Each 1% RVT associated with a 0.017 hazard ratio increase for EFS. Combining pathologic response from PT and LNs helped differentiate outcomes. When compared with radiographic response and circulating tumor DNA clearance, %RVT best approximated EFS. These findings support pathologic response as an emerging survival surrogate. Further assessment of the full spectrum of %RVT in lung cancer and other tumor types is warranted. ClinicalTrials.gov registration: NCT02998528 .
MGA-seq: robust identification of extrachromosomal DNA and genetic variants using multiple genetic abnormality sequencing
Authors: Da Lin, Yanyan Zou, Xinyu Li, Jinyue Wang, Qin Xiao, Xiaochen Gao, Fei Lin, Ningyuan Zhang, Ming Jiao, Yu Guo, Zhaowei Teng, Shiyi Li, Yongchang Wei, Fuling Zhou, Rong Yin, Siheng Zhang, Lingyu Xing, Weize Xu, Xiaofeng Wu, Bing Yang, Ke Xiao, Chengchao Wu, Yingfeng Tao, Xiaoqing Yang, Jing Zhang, Sheng Hu, Shuang Dong, Xiaoyu Li, Shengwei Ye, Zhidan Hong, Yihang Pan, Yuqin Yang, Haixiang Sun, Gang Cao
Journal: Genome biology (2023)

Genomic abnormalities are strongly associated with cancer and infertility. In this study, we develop a simple and efficient method - multiple genetic abnormality sequencing (MGA-Seq) - to simultaneously detect structural variation, copy number variation, single-nucleotide polymorphism, homogeneously staining regions, and extrachromosomal DNA (ecDNA) from a single tube. MGA-Seq directly sequences proximity-ligated genomic fragments, yielding a dataset with concurrent genome three-dimensional and whole-genome sequencing information, enabling approximate localization of genomic structural variations and facilitating breakpoint identification. Additionally, by utilizing MGA-Seq, we map focal amplification and oncogene coamplification, thus facilitating the exploration of ecDNA's transcriptional regulatory function.